Chemistry 2100
Chapter 22
Proteins
Proteins serve many functions, including the
following.
– 1. Structure: Collagen and keratin are the chief
constituents of skin, bone, hair, and nails.
– 2. Catalysts: Virtually all reactions in living systems
are catalyzed by proteins called enzymes.
– 3. Movement: Muscles are made up of proteins
called myosin and actin.
– 4. Transport: Hemoglobin transports oxygen from
the lungs to cells; other proteins transport
molecules across cell membranes.
– 5. Hormones: Many hormones are proteins, among
them insulin, oxytocin, and human growth
hormone.
Proteins
– 6. Protection: Blood clotting involves the protein
fibrinogen; the body used proteins called
antibodies to fight disease.
– 7. Storage: Casein in milk and ovalbumin in eggs
store nutrients for newborn infants and birds.
Ferritin, a protein in the liver, stores iron.
– 8. Regulation: Certain proteins not only control the
expression of genes, but also control when gene
expression takes place.
• Proteins are divided into two types:
– Fibrous proteins
– Globular proteins
COOH
H2 N
H
R
• nonpolar
• polar / neutral
• acidic / basic
Chirality of -Amino Acids
With the exception of glycine, all proteinderived amino acids have at least one
stereocenter (the -carbon) and are chiral.
– The vast majority of -amino acids have the Lconfiguration at the -carbon.
COOH
N H3 +
CH 3
D-Alanine
COO+
H 3N
H
CH 3
L-Alanine
(Fis cher projections )
COOH
H2 N
H
R
• nonpolar
• polar / neutral
• acidic / basic
Protein-Derived -Amino Acids
Nonpolar side chains (at pH 7.0)
-
COO
NH3
+
COO Phen ylalan ine
(Phe, F)
+
NH3
A lanine
(A la, A)
-
COO
NH3
+
-
+
COO
NH3 +
S
COO
+
-
N
H
NH3 +
-
-
NH3
Leucin e
(Leu, L)
H
COO
Isoleucin e
(Ile, I)
-
-
COO
N
H
COO
NH3
Glycine
(Gly, G)
COO
Meth ion in e
(Met, M)
NH3
+
Prolin e
(Pro, P)
Tryptoph an
(Trp , W)
Valine
(Val, V)
Protein-Derived -Amino Acids
• Polar side chains (at pH 7.0)
-
-
COO
H2 N
O
NH3
As paragine
(As n, N )
+
COO
HS
NH3
O
COO
NH3
Glutamine
(Gln, Q)
+
HO
NH3
+
COO
HO
NH3
+
Serine
(Ser, S)
OH
-
COO
+
-
-
H2 N
Cysteine
(Cys, C)
Tyrosine
(Tyr, Y)
-
COO
NH3
+
Threon in e
(Thr, T)
Protein-Derived -Amino Acids
Acidic and basic side chains (at pH 7.0)
-
COO-
O
O
NH3 +
As partic acid
(As p, D )
NH2 +
H2 N
O
-
O
COO-
N
H
NH3 +
COO- Glutamic acid
NH3
+
(Glu, E)
N
N
H
+
H3 N
Arginin e
(Arg, R)
COONH3
+
COONH3
+
Histidine
(His , H)
Lysine
(Lys, K)
essential amino acids
Leu, Ile, Lys, Met, Phe, Thr, Trp, Val, His
( Arg, Tyr, Cys )
COOH
H3 N
H
R
COOH
H3O+
H32 N
H
R
zwitte rion
COO
OH-
H2 N
H
R
Ionization vs. pH
The net charge on an amino acid depends on
the pH of the solution in which it is dissolved.
– If we dissolve an amino acid in water, it is present
in the aqueous solution as its zwitterion.
– If we add a strong acid such as HCl to bring the pH
of the solution to 0.0, the strong acid donates a
proton to the -COO- of the amino acid turning the
zwitterion into a positive ion.
O
+
+
H3 N-CH-C-O + H3 O
R
O
+
H3 N-CH-C-OH + H2 O
R
Ionization vs. pH
– If we add a strong base such as NaOH to the
solution and bring its pH to 14, a proton is
transferred from the NH3+ group to the base
turning the zwitterion into a negative ion.
O
+
H3 N-CH-C-O + OH
R
O
H2 N-CH-C-O + H2 O
R
– To summarize:
O
+
H3 N-CH-C-OH
R
OH
+
H3 O
O
+
H3 N-CH-C-O
R
OH
+
H3 O
O
H2 N-CH-C-OR
Problem: Calculate the net charge of lysine at pH = 3, 7, 11. Estimate pI for lysine.
COOH
H2N
H
CH 2 CH 2 CH 2 CH 2 NH 2
COOH
H2N
H
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
(–)
COOH
H2N
H
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
(–)
COOH
(+)
H2N
H
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
(–)
COOH
(+)
H2N
H
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
(–)
COOH
H2N
H
CH 2 CH 2 CH 2 CH 2 NH 2
COOH
(+)
H2N
H
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
(–)
COOH
H2N
H
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 3
COOH
(+)
H2N
H
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
(–)
COOH
(+)
H2N
COOH
(+)
H
H2N
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 3
H
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
(–)
COOH
(+)
H2N
COOH
(+)
H
H2N
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 3
COOH
H
H2N
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
H
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 11
(–)
COOH
(+)
H2N
COOH
(+)
H
H2N
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 3
(–)
COOH
H
H2N
(+)
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 7
H
CH 2 CH 2 CH 2 CH 2 NH 2
pH = 11
Isoelectric Point (pI)
• Isoelectric
point, pI:
The pH at
which the
majority of
molecules of
a compound
in solution
have no net
charge.
N on polar &
polar s ide chain s
alan ine
as paragin e
cysteine
glutamine
glycine
isoleucine
leu cine
meth ion ine
phen ylalan in e
prolin e
s erin e
threon ine
tyros in e
tryptoph an
valin e
pI
6.01
5.41
5.07
5.65
5.97
6.02
5.98
5.74
5.48
6.48
5.68
5.87
5.66
5.88
5.97
A cidic
pI
S ide Chains
asp artic acid 2.77
glutamic acid 3.22
Basic
Sid e Ch ain s
argin ine
h istidine
lysine
pI
10.76
7.59
9.74
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of
alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of
alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of
alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)
Problem: Predict the electrophoresis behavior at pH 6.0 of a mixture of
alanine (pI 6.0), aspartic acid (pI 2.8) and lysine (pI 9.7)
Lys Ala Asp
Peptide Bonds
O
O
H2 N CH C OH + H2 N CH C OH
R
R'
( - HOH)
O
O
H2 N CH C NH CH C OH
R
R'
Peptide Bonds
O
O
H2 N CH C OH + H2 N CH C OH
R
R'
( - HOH)
O
O
H2 N CH C NH CH C OH
R
R'
Peptide Bonds
O
O
H2 N CH C OH + H2 N CH C OH
R
R'
( - HOH)
O
O
H2 N CH C NH CH C OH
R
R'
Peptide Bonds
O
O
H2 N CH C OH + H2 N CH C OH
R
R'
( - HOH)
O
O
H2 N CH C NH CH C OH
R
R'
Peptide Bonds
O
O
H2 N CH C OH + H2 N CH C OH
R
R'
( - HOH)
O
O
H2 N CH C NH CH C OH
R
R'
H
O
N
C

C
R
H
C
N
H
R'
H
H

N
O

R""
H
C
C
C
C
N
O
R" H
H

H
N
O

C
C
O
R"" H
C
H
O
N
C

C
R
H
C
N
H
R'
H
H

N
O

R""
H
C
C
C
C
N
O
R" H
H

H
N
O

C
C
O
R"" H
C
H
O
N
C

C
R
H
C
N
H
R'
H
H

N
O

R""
H
C
C
C
C
N
O
R" H
H

H
N
O

C
C
O
R"" H
C
H
O
N
C

C
R
H
C
N
H
R'
H
H

N
O

R""
H
C
C
C
C
N
O
R" H
H

H
N
O

C
C
O
R"" H
C
H
O
N
C

C
R
H
C
N
H
R'
H
H

N
O

R""
H
C
C
C
C
N
O
R" H
H

H
N
O

C
C
O
R"" H
C
(N-terminus)
(+)
H2 N CH
O
O
C
(+)
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(C-terminus)
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
(CH 2 ) 3 NHCNH 2
(+)
lysylserylmethionylaspartylarginine
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
(+)
H2 N CH
O
O
C
(+)
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(C-terminus)
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
(CH 2 ) 3 NHCNH 2
(+)
lysylserylmethionylaspartylarginine
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
(+)
H2 N CH
O
O
C
(+)
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(C-terminus)
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
(CH 2 ) 3 NHCNH 2
(+)
lysylserylmethionylaspartylarginine
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
(+)
H2 N CH
O
O
C
(+)
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(C-terminus)
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
(CH 2 ) 3 NHCNH 2
(+)
lysylserylmethionylaspartylarginine
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
(+)
H2 N CH
O
O
C
(+)
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(C-terminus)
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
(CH 2 ) 3 NHCNH 2
(+)
lysylserylmethionylaspartylarginine
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
H2 N CH
O
O
C
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
lysylserylmethionylaspartylarginine
pH = 7
(C-terminus)
(CH 2 ) 3 NHCNH 2
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
(+)
H2 N CH
O
O
C
(+)
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(C-terminus)
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
(CH 2 ) 3 NHCNH 2
(+)
lysylserylmethionylaspartylarginine
pH = 7
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
(+)
H2 N CH
O
O
C
(+)
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(C-terminus)
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
(CH 2 ) 3 NHCNH 2
(+)
lysylserylmethionylaspartylarginine
pH = 3
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
(+)
H2 N CH
O
O
C
(+)
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(C-terminus)
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
(CH 2 ) 3 NHCNH 2
(+)
lysylserylmethionylaspartylarginine
pH = 3
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
H2 N CH
O
O
C
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
lysylserylmethionylaspartylarginine
pH = 11
(C-terminus)
(CH 2 ) 3 NHCNH 2
[Lys–Ser–Met–Asp–Arg]
NH
(N-terminus)
H2 N CH
O
O
C
NH CH
(CH 2 ) 4 NH2
O
C NH CH
CH 2 OH
C
O
NH CH
O
(–)
C
NH CH C OH
(–)
CH 2 CH 2 SCH 3 CH 2 COOH
lysylserylmethionylaspartylarginine
pH = 11
(C-terminus)
(CH 2 ) 3 NHCNH 2
[Lys–Ser–Met–Asp–Arg]
NH
Lys – Ser – Met – Asp – Arg
H2O
H+ or OH-
Arg + Asp + Lys + Met + Ser
(5!) = 120 combinations
(20!) = 2.4  1018 eicosapeptides
(205) = 3.2  106 possible pentapeptide
Lys – Ser – Met – Asp – Arg
H2O
H+ or OH-
Arg + Asp + Lys + Met + Ser
(5!) = 120 combinations
(20!) = 2.4  1018 eicosapeptides
(205) = 3.2  106 possible pentapeptide
Lys – Ser – Met – Asp – Arg
H2O
H+ or OH-
Arg + Asp + Lys + Met + Ser
(5!) = 120 combinations
(20!) = 2.4  1018 eicosapeptides
(205) = 3.2  106 possible pentapeptide
Lys – Ser – Met – Asp – Arg
H2O
H+ or OH-
Arg + Asp + Lys + Met + Ser
(5!) = 120 combinations
(20!) = 2.4  1018 eicosapeptides
(205) = 3.2  106 possible pentapeptide
Lys – Ser – Met – Asp – Arg
H2O
H+ or OH-
Arg + Asp + Lys + Met + Ser
(5!) = 120 combinations
(20!) = 2.4  1018 eicosapeptides
(205) = 3.2  106 possible pentapeptide
Lys – Ser – Met – Asp – Arg
H2O
H+ or OH-
Arg + Asp + Lys + Met + Ser
(5!) = 120 combinations
(20!) = 2.4  1018 eicosapeptides
(205) = 3.2  106 possible pentapeptides
S
H2 N
S
O
Cys
Cys
Tyr
Asn
Ile
Pro
Leu Gly
C NH2
oxytocin
Gln
S
H2 N
S
O
Cys
Cys
Tyr
Asn
Phe
Gln
Pro
Arg
Gly
vasopressin
C NH2
Enkephalins
CH 3
H
N
H
O
HO
OH
Morphine
NH2
C NH
O
HO
CH 3
H
H
CH C NH CH
O
CH2
CH 2 CHCH 3
C NH CH C NH CH C
O
Tyr–Gly–Gly–Phe–Met
Tyr–Gly–Gly–Phe–Leu
Methionine
enkephalin
Leucine enkephalin
O
O
OH
Insulin
S
5
S
10
15
20
Gly–Ile–Val–Glu–Gln–Cys–Cys–Thr–Ser–Ile–Cys–Ser–Leu–Tyr–Gln–Leu–Glu–Asn–Tyr–Cys–Asn
S
S
5
S
10
15
S
20
25
Phe–Val–Asn–Gln–His–Leu–Cys–Gly–Ser–His–Leu–Val–Glu–Ala–Leu–Tyr–Leu–Val–Cys–Gly–Glu–Arg–Gly–Phe–Phe–Tyr–Thr–Pro–Lys–Thr
30
Structure of Proteins
O
N
CH
H
R
C
O
N
CH
H
R"
C
O
N
CH
H
R'
O
C N
CH
H
R"
O
O
N
CH
C N
H
R"
""
H
CH
R
C
C
O
N
CH
H
R
C
O
N
CH
H
R"
C
O
N
CH
H
R'
O
C N
CH
H
R"
O
O
N
CH
C N
H
R"
""
H
CH
R
C
C
O
N
CH
H
R
C
O
N
CH
H
R"
C
O
N
CH
H
R'
O
C N
CH
H
R"
O
O
N
CH
C N
H
R"
""
H
CH
R
C
C
O
N
CH
H
R
C
O
N
CH
H
R"
C
O
N
CH
H
R'
O
C N
CH
H
R"
O
O
N
CH
C N
H
R"
""
H
CH
R
C
C
Secondary Structure: The -Helix
-Pleated Sheet
Random Coil
-pleated sheet
-helix
-pleated sheet
-helix
Protein Tertiary Structure
-pleated sheet
-helix
-pleated sheet
-helix
-pleated sheet
salt bridge
-O
O
C
NH3+
-helix
-pleated sheet
-helix
-pleated sheet
salt bridge
O
-O
C
NH3+
CH2
O
H
-helix
hydrogen
bond
O
H
CH2
-pleated sheet
-helix
-pleated sheet
hydrogen
bond
H N
OH
H
C O
salt bridge
O
-O
C
NH3+
CH2
O
H
-helix
hydrogen
bond
O
H
CH2
-pleated sheet
-helix
hydrophilic
interaction
to water
-pleated sheet
HO
CH 2
N H2
HO
O
C
hydrogen
bond
C H2
H N
OH
CH2
H
C O
salt bridge
O
-O
C
NH3+
CH2
O
H
-helix
hydrogen
bond
O
H
CH2
-pleated sheet
-helix
hydrophilic
interaction
to water
-pleated sheet
-helix
HO
CH 2
CH2
N H2
HO
O
C
hydrogen
bond
C H2
H N
OH
CH2
H
hydrophobic
interaction
C O
salt bridge
CH2
O
-O
C
NH3+
CH2
O
H
-helix
hydrogen
bond
O
H
CH2
-pleated sheet
hydrophilic
interaction
to water
-pleated sheet
-helix
HO
CH 2
CH2
N H2
HO
O
C
hydrogen
bond
C H2
H N
OH
CH2
H
hydrophobic
interaction
C O
salt bridge
CH2
O
-O
C
NH3+
CH2
O
H
-helix
hydrogen
bond
O
H
CH
CH3 CH3
CH2
-pleated sheet
CH3
hydrophilic
interaction
to water
-pleated sheet
-helix
HO
CH 2
CH2
N H2
HO
O
C
hydrogen
bond
C H2
H N
OH
CH2
CH
CH3 CH3
hydrophobic
interaction
H
C O
salt bridge
O
-O
S
C
S
NH3+
CH2
CH2
disulfide
bond
S
S
O
H
-helix
hydrogen
bond
O
H
CH2
-pleated sheet
CH3
Protein Quaternary Structure
Hemoglobin
C3032H4816N735O780S8Fe4 (MW 64,450)
Sickle-Cell Anemia
Sequence Varies: Ask 23andMe
Proteins
Denaturation
Denaturation… also known
as “Cooking”
Misfolding Diseases
Mutation Impairs Proper Folding
Sickle Cell
Anemia
Cystic Fibrosis
Contagious Misfolding: Prions